US8772341B2 - Compositions for the treatment of hoof diseases - Google Patents

Compositions for the treatment of hoof diseases Download PDF

Info

Publication number
US8772341B2
US8772341B2 US12/440,405 US44040507A US8772341B2 US 8772341 B2 US8772341 B2 US 8772341B2 US 44040507 A US44040507 A US 44040507A US 8772341 B2 US8772341 B2 US 8772341B2
Authority
US
United States
Prior art keywords
aminopropyl
bis
acid
hoof
manure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related, expires
Application number
US12/440,405
Other versions
US20100286270A1 (en
Inventor
Chris Foret
Alex Skender
Thomas C. Hemling
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DeLaval Holding AB
Original Assignee
DeLaval Holding AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by DeLaval Holding AB filed Critical DeLaval Holding AB
Priority to US12/440,405 priority Critical patent/US8772341B2/en
Assigned to DELAVAL HOLDING AB reassignment DELAVAL HOLDING AB ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FORET, CHRIS, HEMLING, THOMAS C., SKENDER, ALEX
Publication of US20100286270A1 publication Critical patent/US20100286270A1/en
Application granted granted Critical
Publication of US8772341B2 publication Critical patent/US8772341B2/en
Expired - Fee Related legal-status Critical Current
Adjusted expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to compositions and methods for the control of hoof diseases.
  • solutions effective in treating or preventing papillomatous digital dermatitis, interdigital phlegmon, interdigital dermatitis, laminitis, white line disease, heel erosion and other hoof diseases are disclosed.
  • Infectious diseases of the hooves such as hairy hoof warts (papillomatous digital dermatitis, or “PDD”), hoof rot (interdigital phlegmon), stable hoof rot (interdigital dermatitis), laminitis, white line disease and heel erosion are common in farm animals such as sheep, goats, horses, dairy cows and beef cattle. These diseases are a significant source of lameness, and produce a large economic and humane impact on the farming industry.
  • PDD hairy hoof warts
  • hoof rot interdigital phlegmon
  • stable hoof rot interdigital dermatitis
  • laminitis white line disease and heel erosion
  • PDD is an infection of the epidermis of an animal's digit that is believed to be caused by Treponema organisms, which survive under the skin in conditions of low oxygen, temperatures between 30° C. and 37° C., and a pH range of 7.2 to 7.4.
  • PDD infections range from painful, moist lesions to raised, hairy, wart-like lesions that can result in severe lameness, and even death, if not properly treated. With respect to dairy cows, hoof warts are also associated with losses in milk production, reproductive efficiency and body weight.
  • Hoof rot, or interdigital phlegmon is an infection of the soft tissue between the claws of the feet, where bacteria invade the skin of the foot at injured or damaged skin areas.
  • the infection causes a painful swelling of the skin between the claws. A fissure or crack then develops along the swollen area for part or all of the length of the interdigital space. If left untreated, hoof rot can enter the joints, bones, and/or tendons of the foot, making recovery from the infection unlikely. Animals with hoof rot can have a mild fever, loss of appetite and accompanying weight loss, and develop mild to severe lameness. Interdigital dermatitis, or stable hoof rot, is generally a chronic inflammation of the skin in the interdigital cleft. The condition may cause lameness or heel crack/heel erosion.
  • hoof diseases papillomatous digital dermatitis, interdigital phlegmon and interdigital dermatitis—are caused by bacterial infections, and they may be accompanied by or lead to complications with other hoof diseases such as laminitis, white line disease and heel erosion.
  • germicides to treat or prevent hoof diseases is also common.
  • germicidal compositions containing copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid are known.
  • antibiotic or germicidal compositions are typically carried out by making the animals walk through a footbath.
  • the solution becomes contaminated with manure.
  • Many formulas that are currently used for footbath solutions loose their activity in the presence of manure.
  • these baths can become a breeding ground for bacteria, and can accelerate the spread of infectious hoof diseases, rather than prevent them.
  • Infectious hoof diseases can also be treated by a topical spray, footwrap or application of a foam or gel.
  • the hoof is likely to be highly contaminated with manure, dirt or other soils before and/or shortly after application.
  • germicides such as iodine or chlorine
  • iodine or chlorine are extremely effective disinfectants for other purposes, but they are not useful for a footbath solution because they quickly react with manure, which reduces the efficacy of the active ingredients.
  • Germicides such as salicylic acid are also ineffective for footbath solutions due to limited solubility.
  • the present invention advances the art and overcomes the problems outlined above by providing highly efficacious disinfectant solutions for the treatment and/or prevention of hoof diseases.
  • the disclosed solutions are substantially unaffected by the presence of manure, and may be used on hooves in their natural (uncleaned) state. Methods for using the solutions to treat or prevent hoof diseases are disclosed.
  • an aqueous composition for treatment or prevention of infectious hoof diseases includes a therapeutically effective amount of an N,N-bis(3-aminopropyl) C 6 -C 18 alkyl amine, wherein the composition retains germicidal activity in the presence of greater than 10% manure.
  • an aqueous composition for treatment or prevention of infectious hoof diseases consists essentially of a therapeutically effective amount of an N,N-bis(3-aminopropyl) C 6 -C 18 alkyl amine, wherein the composition retains germicidal activity in the presence of greater than 10% manure.
  • a method for treating or preventing infectious hoof diseases includes topically administering a therapeutically effective amount of an aqueous composition comprising an N,N-bis(3-aminopropyl) C 6 -C 18 alkyl amine to one or more hooves of an animal, wherein the step of administering occurs with the hoof or hooves in a natural state.
  • compositions and methods for treating or preventing hoof diseases There will now be shown and described compositions and methods for treating or preventing hoof diseases.
  • Concentrations disclosed throughout this application are based on ready-to-use compositions, except where otherwise stated. Those of skill in the art will appreciate that such compositions may be manufactured and/or sold in concentrated forms that are suitable for dilution prior to use. Manipulation of the concentration of the disclosed compositions is within the level of ordinary skill in the art.
  • an aqueous composition for the treatment or prevention of infectious hoof diseases contains a germicide.
  • the germicide may be present in an amount from about 0.03% to about 90% by weight of the composition, or from about 0.03% to about 50% by weight, or from about 0.03% to about 30% by weight, or from about 0.03% to about 2% by weight, or from about 0.1% to about 1% by weight, and may be used to treat animal hooves that are presented in their natural state. Hooves in their natural state may be soiled with particulate matter, such as dirt and manure, and/or microscopic pathogens, such as bacteria. For example, the present compositions remain effective in the presence of greater than 10% manure, or greater than 20% manure. Use of the present compositions on hooves in their natural state eliminates the need for a pre-treatment or pre-cleaning step, and therefore provides a significant cost and time advantage over known compositions.
  • a composition for the treatment or prevention of hoof diseases comprises an effective amount of an N,N-bis(3-aminopropyl) C 6 -C 18 alkyl amine, and optionally additional germicides selected from the group consisting of bronopol, chlorhexidine salts, C 6 -C 12 fatty acids, triclosan, glycolic acid, lactic acid, polyhexamethyl biguanide, polyhexamethylene guanidine hydrochloride, polyhexamethylene guanidine hydrophosphate, poly[2-(2-ethoxy)-ethoxyethyl]-guanidinium chloride, benzyl alcohol, benzoic acid and mixtures thereof.
  • additional germicides selected from the group consisting of bronopol, chlorhexidine salts, C 6 -C 12 fatty acids, triclosan, glycolic acid, lactic acid, polyhexamethyl biguanide, polyhexamethylene guanidine hydrochloride, polyhexamethylene guanidine hydro
  • an aqueous composition for the treatment or prevention of infectious hoof diseases consists essentially of an effective amount of an N,N-bis(3-aminopropyl) C 6 -C 18 alkyl amine, and optionally additional ingredients that do not materially alter the germicidal properties of the composition.
  • additional ingredients may include one or more of a pH adjusting agent, a wetting agent, a foaming agent, a dye, a viscosity control agent, a preservative, a skin conditioning agent, a coupling agent and a solvent.
  • compositions provide a substantial reduction, e.g., greater than 99% or preferably 99.99%, in Gram positive and Gram negative bacterial populations.
  • Exemplary bacteria that contribute to hoof infections include Bacteroides spp, Bacteriodes melaningenicus, Campylobacter faecalis, Clostridium spp, Fusobacterium spp, Peptococcus asaccharolyticus, Peptostreptococcus spp, Serpens spp, Treponema spp, Bacteroides thetaictaomicron, Fusobacterium necrophorum, Prevotella melaminogenicus, Porphyromonas asaccharolytica, Porphyromonas levii, Porphyromonas melaminogenicus, Dichelobacter fragilis, Arcanobacterium pyogenes, Dichelobacter nodosus and Porphyromonas necrophorum .
  • compositions may be acidic (pH less than about 5) or near neutral with pH from about 5 to about 10.
  • pH may be adjusted to any value that is desired in the intended environment of use by the addition of acid, base or buffer.
  • a broader object of the disclosed instrumentalities is to provide a germicidal composition that may be used, for example, according to any purpose for antibacterial or bactericidal properties.
  • the composition is intended to be used as a footbath for treating animal hooves.
  • the composition is intended to be used as a hand sanitizer, a skin cleanser, a surgical scrub, a wound care agent, a disinfectant, a bath/shower gel, a hard surface sanitizer and the like.
  • Preferred compositions for skin applications have a pH of about 2.5 to about 10 and provide a substantial reduction, e.g., greater than 99%, in Gram positive and Gram negative bacterial populations.
  • the compositions have a pH in the range of about 5 to 10. Further, different uses may prompt different pH targets. For example, compositions adapted for hard surfaces may exhibit low pH values, such as 1.0 or 0.5.
  • terapéuticaally effective amount is intended to qualify the amount of the topical composition which will achieve the goal of decreased microbial concentration. “Therapeutically effective” may also refer to improvement in disorder severity or the frequency of incidence over no treatment.
  • topical shall refer to any composition which may be applied to the epidermis, keratin or other animal portion.
  • additive shall mean any component that is not a germicide or a solvent used to dilute or solubilize the components of the composition.
  • E. coli and S. aureus were chosen as representative bacteria for screening purposes. Solutions of the mixtures with 10% manure and bacteria were prepared, and the reduction in the concentration of bacteria was determined after 30 seconds and again after 5 minutes. In addition, the formulas were evaluated for skin irritation based on in vitro test data. The testing method used was that of Wolfgang J. W. Pape, Udo Hoppe: In vitro Methods for the Assessment of Primary Local Effects of Topically Applied Preparations. Skin Pharmacol . (1991), 4: 205-212, which is incorporated herein by reference. Based on this data, various components were selected for use in aqueous disinfectant solutions, such as footbaths.
  • a preferred composition includes from 0.001% to 90% by weight of at least one germicide.
  • germicide shall be used to describe a composition which, when used alone or in combination with other germicides, accelerates the demise or limits the growth or replication of microorganisms, particularly bacteria.
  • germicides include N,N-bis(3-aminopropyl) C 6 -C 18 alkyl amines (such as N,N-bis(3-aminopropyl)dodecylamine), bronopol (2-bromo-2-nitro-1,3-propanediol), chlorhexidine salts, C 6 -C 12 fatty acids, triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether, may be purchased from Ciba Specialty Chemicals as IRGASANTM and IRGASAN DP 300TM), glycolic acid, lactic acid, benzyl alcohol, benzoic acid, polyhexamethyl biguanide (CAS 32289-58-0), guanidine salts such as polyhexamethylene guanidine hydrochloride (CAS 57028-96-3), polyhexamethylene guanidine hydrophosphate (89697-78-9), and poly[2-(2-ethoxy)-ethoxyethoxye
  • the disclosed germicides may be used in combination with traditional germicides such as copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid, for example, to achieve an effective kill at lower concentrations of traditional germicides.
  • traditional germicides such as copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid, for example, to achieve an effective kill at lower concentrations of traditional germicides.
  • a composition includes from 0.2% to 90% by weight of at least one acid.
  • Acids for use in the present compositions are selected for their efficacy against microorganisms, particularly bacteria, and minimal irritation of the skin.
  • suitable acids include sulfuric acid, sulfurous acid, sulfamic acid, hydrochloric acid, phosphoric acid, phosphorous acid, C 1 -C 4 fatty acids, citric acid, glycolic acid, lactic acid, acetic acid, benzoic acid, malic acid, oxalic acid, tartaric acid, succinic acid, glutaric acid, valeric acid and the like.
  • compositions may be supplemented by buffering agents, pH adjusting agents, emollients, preservatives, surfactants or wetting agents, dyes, foaming agents, viscosity modifying agents, stabilizers, perfumes, co-solvents, coupling agents and mixtures thereof. These may be present in any suitable amount.
  • the pH value of the composition may be adjusted by the addition of acidic, basic or buffering agents.
  • Suitable acids for use as pH adjusting agents may include, for example, sulfuric acid, sulfurous acid, sulfamic acid, hydrochloric acid, phosphoric acid, phosphorous acid, C 1 -C 4 fatty acids, citric acid, glycolic acid, lactic acid, acetic acid, benzoic acid, malic acid, oxalic acid, tartaric acid, succinic acid, glutaric acid, valeric acid and the like.
  • the pH may be raised, or made more alkaline, by addition of an alkaline agent such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof.
  • Traditional acid buffering agents such as citric acid, lactic acid and phosphoric acid may also be used to maintain a desired pH.
  • wetting agents or surfactants may be included in the disclosed formulations. Typical wetting agents are used to wet the surface of application, thereby reducing surface tension so that the product can easily contact the surface.
  • the wetting agents or surfactants of the formulation increase overall detergency of the formula, solubilize or emulsify organic ingredients that otherwise would not dissolve or emulsify, and facilitate penetration of active ingredients deep into depressions of the surface, which may be an animal hoof.
  • Suitably effective surfactants may include anionic, cationic, nonionic, zwitterionic and amphoteric surfactants.
  • Wetting agents and surfactants suitable for use in the disclosed formulations can be high foaming, low foaming and non-foaming.
  • Suitable anionic surfactants can be chosen from alkyl sulfonic acid, an alkyl sulfonate salt, a linear alkyl benzene sulfonic acid, a linear alkyl benzene sulfonate, an alkyl ⁇ -sulfomethyl ester, an ⁇ -olefin sulfonate, an alcohol ether sulfate, an alkyl sulfate, an alkylsulfo succinate, a dialkylsulfo succinate, or alkali metal, alkaline earth metal, amine and ammonium salts thereof.
  • linear C 10 -C 16 alkylbenzene sulfonic acid linear C 10 -C 16 alkylbenzene sulfonate or alkali metal, alkaline earth metal, amine and ammonium salts thereof, e.g., sodium dodecylbenzene sulfonate, sodium C 14 -C 16 ⁇ -olefin sulfonate, sodium methyl ⁇ -sulfomethyl ester and disodium methyl ⁇ -sulfo fatty acid salts.
  • Suitable nonionic surfactants can be chosen from alkyl polyglucoside, alkyl ethoxylated alcohol, alkyl propoxylated alcohol, ethoxylated-propoxylated alcohol, sorbitan, sorbitan ester and alkanol amide.
  • Pluronic® poloxamers commercialized by BASF Chemical Co.
  • Amphoteric surfactants can be chosen from alkyl betaines and alkyl amphoacetates.
  • Suitable betaines include cocoamidopropyl betaine
  • suitable amphoacetates include sodium cocoamphoacetate, sodium lauroamphoacetate and sodium cocoamphodiacetate.
  • a foaming agent may be used in the disclosed antimicrobial compositions.
  • a foaming agent aerates a liquid composition to produce a foam that may increase surface area of the composition and improve adherence with the surface to be treated (e.g., an animal hoof).
  • a high foaming surfactant such as sodium lauryl sulfate, dodecylbenzene sulfonic acid, sodium alkylaryl polyether sulfate, sodium lauryl ether sulfate, sodium decyl sulfate, cocamine oxide, C 12 -C 14 whole coconut amido betaines can be used to generate a stable foam.
  • the foam is produced when agitation in the form of a compressed gas is mixed with the solution either by bubbling the gas into the solution or spraying the solution or solution-gas mixture through spray equipment.
  • gases include but are not limited to nitrogen, air, carbon dioxide and mixtures thereof.
  • Foam can also be generated by the mechanical action of animals walking through the composition, or by other mechanical means that mix atmospheric air with the composition.
  • the composition can be applied by having animals walk through an area containing the foam or by having the animal walk through a footbath solution that has foam floating on top of the solution.
  • One or more dyes may be included in the composition. Color on an animal's hoof or hooves may serve as an indicator that a particular animal has been treated. To preclude any problems with possible contamination of milk, for example, in the event that the dye contacts the animal's teats or enters the animal's circulatory system, only FD&C Certified (food grade) dyes should be used. There are many FD&C dyes available, such as FD&C Red #40, FD&C Yellow #6, FD&C Yellow #5, FD&C Green #3, FD&C Blue #1, FD&C Orange #4 and combinations thereof.
  • Solution viscosity may be thinned by the addition of water or co-solvent; however, the compositions, especially gel forms, may benefit from the use of a viscosity modifying agent in an amount generally ranging from 0.1% to about 10% by weight of the composition.
  • Viscosity of the composition preferably ranges from 1 cPs to 10000 cPs at ambient temperature.
  • the viscosity referred to throughout this application is Brookfield viscosity measured in cPs by a Brookfield LV viscometer at ambient temperature (25° C.) with a spindle #2 @ 3 to 30 rpm.
  • a thickener may be added to achieve a viscosity range of from 50 cPs to 10000 cPs, or from 1000 cPs to 4000 cPs.
  • Viscosity modifying agents include plant gum materials such as guar gum; starch and starch derivatives, for example, hydroxyethyl starch or cross-linked starch; microbial polysaccharides, for example, xanthan gum or seaweed polysaccharides, such as sodium alginate, carrageenan, curdlan, pullulan or dextran; whey; gelatin; chitosan; chitosan derivatives; polysulfonic acids and their salts; polyacrylamide; and glycerol.
  • Cellulosic thickeners may be used including hemicellulose, for example arabinoxylanes and glucomannanes; cellulose and derivatives thereof; for example methyl cellulose, ethyl cellulose, hydroxyethyl cellulose or carboxymethyl cellulose.
  • Preservatives may be added to the compositions.
  • ethylenediaminetetraacetic acid (EDTA) and its alkali salts act as chelating agents to bind metal ions that would otherwise facilitate metalloenzyme reactions that produce energy for bacterial cell replication.
  • EDTA ethylenediaminetetraacetic acid
  • Other traditional preservatives are widely used, for example, paraban, methyl paraban, ethyl paraban, glutaraldehyde, etc.
  • Preservatives such as an alcohol can also be added.
  • the alcohol in embodiments, may be benzyl alcohol, a low molecular weight alcohol having a carbon number less than five, and combinations thereof.
  • Skin conditioning agents may also be optionally used in the disclosed compositions. Skin conditioning agents may provide extra protection for human or animal skin prior to or subsequent to being exposed to adverse conditions.
  • skin conditioning agents may include moisturizers, such as glycerin, sorbitol, propylene glycol, Laneth-5 to 100, lanolin alcohol, shea butter and coco butter; sunscreen agents, such as titanium dioxide, zinc oxide, octyl methoxycinnamate (OMC), 4-methylbenzylidene camphor (4-MBC), avobenzone, oxybenzone and homosalate; and itch-relief or numbing agents, such as aloe vera, calamine, mint, menthol, caphor, antihistamines, corticosteroids, benzocaine and paroxamine HCl.
  • moisturizers such as glycerin, sorbitol, propylene glycol, Laneth-5 to 100, lanolin alcohol, shea butter and coco butter
  • sunscreen agents such as titanium
  • a composition may contain a coupling agent that facilitates dissolution of one or more components, e.g., surfactants or fatty acids that would otherwise be insoluble or only sparingly soluble in the solvent.
  • Coupling agents generally contain short chained (C 2 -C 6 ) moieties linked to bulky hydrophilic groups, such as hydroxyl and/or sulfonate groups.
  • Exemplary coupling agents include aryl sulfonates such as sodium naphthalene sulfonate, sodium octane sulfonate, sodium xylene sulfonate, and ammonium octane sulfonate, as well as some phosphate esters.
  • the preferred solvent for the present composition is water.
  • solvents or co-solvents other than water may be used to serve the same purpose.
  • a composition may contain at least about 5% by weight water and preferably at least about 10% by weight water based on the total weight of the composition.
  • Propylene glycol, ethylene glycol, glycerine and alcohols can also be used as solvents either alone or in combination with water.
  • a method for treating or preventing infectious hoof diseases includes topically administering a therapeutically effective amount of an aqueous germicidal composition comprising a germicide, or an acid and a germicide.
  • the composition may be administered as a liquid, a spray, a foam, a gel, an ointment, a cream, a footbath, a footwrap coated with the composition, or any other topical form acceptable to the industry.
  • E. coli E. coli
  • S. aureus ATCC 6538
  • Sterile buffer 0.0003 M phosphate adjusted to pH 6.6
  • S. aureus was then diluted with buffer and transferred to nutrient agar in French bottles, and E. coli was diluted and transferred to fresh nutrient agar tubes. Both types of bacteria were incubated at 37° C. for 72 hours. E. coli was then diluted and transferred to nutrient agar in French bottles.
  • Germicide sample solutions were prepared and dispensed into the flasks containing manure. For tests without manure, 99 mL of germicide were added to an empty, sterile, 250 mL flask. For a 10% manure challenge, 89 mL of germicide were added to a flask prepared with 10 g of manure, and 79 mL of germicide were added to flasks with 20 g of manure for a 20% manure challenge.
  • N,N-bis(3-aminopropyl)dodecylamine was neutralized with a peroxide neutralizer solution containing: tryptic soy powder 30 g/L; lecithin 30 g/L; Tween 80 100 g/L; sodium thiosulfate 5 g/L; and L-histidine 1 g/L diluted to 1 L in a volumetric flask.
  • a peroxide neutralizer solution containing: tryptic soy powder 30 g/L; lecithin 30 g/L; Tween 80 100 g/L; sodium thiosulfate 5 g/L; and L-histidine 1 g/L diluted to 1 L in a volumetric flask.
  • Three serial dilutions were made of this solution and 1 mL of each solution was dispensed into a Petri dish in duplicate. Also, 0.1 mL of the most dilute solution was dispensed in duplicate.
  • the 10 8 cfu/mL bacteria suspensions were diluted to concentrations of 10 4 and 10 3 cfu/mL.
  • concentrations of 10 4 and 10 3 cfu/mL were diluted to concentrations of 10 4 and 10 3 cfu/mL.
  • One milliliter of the 10 4 cfu/mL dilution and 0.1 mL of the 10 3 cfu/mL dilution (done in triplicate) were dispensed onto Petri dishes and approximately 15 mL of tryptone glucose extract agar was added. When solidified, the plates were incubated at 37° C. for 48 hours. An average of the plate counts for the triplicate platings of the 10 3 cfu/mL dilution was considered the initial numbers control count.
  • Irritation tests were performed to determine whether or not the disclosed compositions would be mild enough for topical application. These tests involved two measurements made on fresh calf blood, where red blood cells were isolated by adding 50 mL of sodium citrate buffer (17.03 g trisodium citrate+8.45 g citric acid diluted to 1 L with bacteria-free DI water) to every 450 mL of blood, then repetitively washing with sodium citrate buffer and centrifuging to remove white blood cells and plasma.
  • sodium citrate buffer 17.03 g trisodium citrate+8.45 g citric acid diluted to 1 L with bacteria-free DI water
  • compositions disclosed herein were introduced into a container containing the isolated red blood cells and values for Haemolysis (H 50 ); a Denaturation Index value (DI); and a Lysis/Denaturation Ratio (L/D) were determined using methods disclosed by Wolfgang J. W. Pape, Udo Hoppe: In vitro Methods for the Assessment of Primary Local Effects of Topically Applied Preparations. Skin Pharmacol . (1991), 4: 205-212.
  • the denaturation of protein caused by the test product was measured by the denaturation index (DI).
  • the overall irritation value for a product was determined by the ratio of the H 50 /DI which is referred to as the lysis/denaturation quotient.
  • H 50 value which measures haemolysis alone usually shows a similar irritation correlation to the L/D ratio.
  • a crude scale is H 50 >500 ppm (non-irritant); 120-500 (slight irritant), 30-120 (moderate irritant), 10-30 (irritant) and 0-10 (strong irritant).
  • the DI score which measures denaturation of protein also shows a correlation to the L/D ratio.
  • a crude scale is DI 0-5% (non-irritant); 5-10% (slight irritant), 10-75% (moderate irritant), 75-100% (irritant) and >100% (strong irritant).
  • the L/D ratio is the primary value used to determine irritation.
  • An L/D value greater than 100 is an indication that the formulation is a non-irritant; levels between 10 and 100 are considered slight irritants; levels between 1 and 10 are considered moderate irritants; levels between 0.1 to 1 are considered irritants; and levels lower than 0.1 are considered strong irritants.
  • a practical upper limit for the L/D ratio is about 1,000,000.
  • N,N-bis(3-aminopropyl)dodecylamine when diluted 1+180 with potable water gave >7.97 log reduction (complete kill) for E. coli and >7.94 log reduction for S. aureus after 5 minutes exposure with 10% manure added.
  • This Example shows that N,N-bis(3-aminopropyl)dodecylamine has excellent germicidal properties at concentrations at least as low as 0.1%.
  • NCLS National Clinical Committee for Laboratory Standards
  • BDD Bovine Digital Dermatitis
  • Table 1 Six Bovine Digital Dermatitis (BDD) associated treponeme strains (Table 1) were used to investigate in vitro susceptibility of BDD associated Treponema (Evans, N. J.; Brown, J.; Demirkan, I.; Carter, S. D.; Hart, C. A. “In vitro susceptibility of Bovine Digital Dermatitis associated Treponema to antimicrobial agents” to be submitted to Antimicrob. Agents Chemother. To be submitted for publication September 2007).
  • the strains included two isolates from each of three distinct phylogroups corresponding to three proposed new taxa, Treponema medium subsp. bovis, Treponema bovis and Treponema pedis (Evans, N.
  • Germicidal susceptibility testing was performed using the broth microdilution method previously described by Evans et al., 2007.
  • Ninety-six well sterile polystyrene microplates each including positive controls (bacteria inoculated without germicide), negative controls (no bacteria or germicide) and serial two-fold dilutions of each composition to be tested, all in oral treponeme enrichment broth (OTEB; Anearobe Systems, CA, USA) inclusive of the respective serum supplement, were used.
  • the respective OTEB serum supplements were 10% (v/v) fetal calf serum (FCS) for T. bovis and T. pedis strains and 10% (v/v) rabbit serum (RS) for T. medium subsp.
  • bovis strains Microplates were incubated in an anaerobic cabinet overnight prior to use. The T. pedis, T. medium subsp. bovis and T. bovis strain inoculums were taken from cultures grown for 4, 6 and 7 days respectively with all cultures being grown at 36° C. under anaerobic conditions in OTEB supplemented with respective serums. An inoculation volume of 50 ⁇ l was used for all three taxa. Each well, prior to inoculation, had a volume of 150 ⁇ l resulting in a final volume, after inoculation, of 200 ⁇ l.
  • absorbance at 540 nm was measured for the microplate wells using a Multiskan microtitre plate reader (Thermo Scientific, Hampshire, U.K.). Measurements were recorded before and after incubation at 36° C. under anaerobic conditions—three days for T. pedis strains and four days for T. bovis and T. medium subsp. bovis strains. The MIC for each germicide was taken as the lowest concentration of germicide that prevented growth. Cell growth was determined by comparison of the absorbance measurement immediately before and after incubation. The MIC values were taken as the median of three experiments performed on different days.
  • MBC values For determination of MBC values for each germicide, after MIC determination, 25 ⁇ l of culture from the MIC well and the next three wells of increased germicide concentration were subcultured to new wells containing 175 ⁇ l OTEB with the respective serum supplement but no germicide. Microplates were incubated for a further four days at 36° C. under anaerobic conditions. Growth was assessed using phase contrast microscopy. The MBC value was defined as the dilution that contained no treponeme cells in the subcultured media. The MBC values are reported as the median of three experiments performed on different days.
  • the average MBC for copper sulfate was 0.0054% w/w and the average MEC for formaldehyde was 0.0094% w/w. This confirms that copper sulfate and formaldehyde are effective against Treponema organisms. However, it was determined that N,N-bis(3-aminopropyl)dodecylamine was effective at a concentration about a factor of one lower. The MBC for N,N-bis(3-aminopropyl)dodecylamine was 0.00051% w/w.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Zoology (AREA)
  • Dispersion Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Environmental Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Virology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)
  • Toxicology (AREA)

Abstract

Germicidal compositions containing one or more N,N-bis(3-aminopropyl) C6-C18 alkyl amines, such as N,N-bis(3-aminopropyl)dodecylamine, and methods of using the compositions for treatment or prevention of infectious hoof diseases are disclosed. The germicidal compositions remain active in the presence of manure, which eliminates the need to pre-clean the hooves before use, and have particular utility for treating or preventing papillomatous digital dermatitis, interdigital phlegmon, interdigital dermatitis, laminitis, white line disease, heel erosion and other hoof diseases.

Description

RELATED APPLICATIONS
This application claims the benefit of priority to commonly-owned U.S. Provisional Patent Application Nos. 60/843,113, filed 8 Sep. 2006, and 60/888,243, filed 5 Feb. 2007, each of which is incorporated herein by reference.
BACKGROUND
1. Field of the Invention
The present invention relates to compositions and methods for the control of hoof diseases. In particular, solutions effective in treating or preventing papillomatous digital dermatitis, interdigital phlegmon, interdigital dermatitis, laminitis, white line disease, heel erosion and other hoof diseases are disclosed.
2. Description of the Related Art
Infectious diseases of the hooves, such as hairy hoof warts (papillomatous digital dermatitis, or “PDD”), hoof rot (interdigital phlegmon), stable hoof rot (interdigital dermatitis), laminitis, white line disease and heel erosion are common in farm animals such as sheep, goats, horses, dairy cows and beef cattle. These diseases are a significant source of lameness, and produce a large economic and humane impact on the farming industry.
PDD is an infection of the epidermis of an animal's digit that is believed to be caused by Treponema organisms, which survive under the skin in conditions of low oxygen, temperatures between 30° C. and 37° C., and a pH range of 7.2 to 7.4. PDD infections range from painful, moist lesions to raised, hairy, wart-like lesions that can result in severe lameness, and even death, if not properly treated. With respect to dairy cows, hoof warts are also associated with losses in milk production, reproductive efficiency and body weight. Hoof rot, or interdigital phlegmon, is an infection of the soft tissue between the claws of the feet, where bacteria invade the skin of the foot at injured or damaged skin areas. Initially, the infection causes a painful swelling of the skin between the claws. A fissure or crack then develops along the swollen area for part or all of the length of the interdigital space. If left untreated, hoof rot can enter the joints, bones, and/or tendons of the foot, making recovery from the infection unlikely. Animals with hoof rot can have a mild fever, loss of appetite and accompanying weight loss, and develop mild to severe lameness. Interdigital dermatitis, or stable hoof rot, is generally a chronic inflammation of the skin in the interdigital cleft. The condition may cause lameness or heel crack/heel erosion. These three hoof diseases—papillomatous digital dermatitis, interdigital phlegmon and interdigital dermatitis—are caused by bacterial infections, and they may be accompanied by or lead to complications with other hoof diseases such as laminitis, white line disease and heel erosion.
Treatment or prevention of hoof diseases generally involves topical application of antibiotics to affected areas. However, antibiotics are expensive, and, particularly when treating cattle, concerns related to the presence of antibiotics in beef and milk arise. Further, it is well known that extended use of antibiotics leads to antibiotic-resistance, and the development of more aggressive strains of bacteria.
The use of chemical germicides to treat or prevent hoof diseases is also common. For example, germicidal compositions containing copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid are known.
Application of the antibiotic or germicidal compositions is typically carried out by making the animals walk through a footbath. However, after a few animals have passed through the footbath, the solution becomes contaminated with manure. Many formulas that are currently used for footbath solutions loose their activity in the presence of manure. As a result, these baths can become a breeding ground for bacteria, and can accelerate the spread of infectious hoof diseases, rather than prevent them. Infectious hoof diseases can also be treated by a topical spray, footwrap or application of a foam or gel. However, the hoof is likely to be highly contaminated with manure, dirt or other soils before and/or shortly after application.
Other germicides, such as iodine or chlorine, are extremely effective disinfectants for other purposes, but they are not useful for a footbath solution because they quickly react with manure, which reduces the efficacy of the active ingredients. Germicides such as salicylic acid are also ineffective for footbath solutions due to limited solubility.
SUMMARY
The present invention advances the art and overcomes the problems outlined above by providing highly efficacious disinfectant solutions for the treatment and/or prevention of hoof diseases. The disclosed solutions are substantially unaffected by the presence of manure, and may be used on hooves in their natural (uncleaned) state. Methods for using the solutions to treat or prevent hoof diseases are disclosed.
In one embodiment, an aqueous composition for treatment or prevention of infectious hoof diseases includes a therapeutically effective amount of an N,N-bis(3-aminopropyl) C6-C18 alkyl amine, wherein the composition retains germicidal activity in the presence of greater than 10% manure.
In one embodiment, an aqueous composition for treatment or prevention of infectious hoof diseases consists essentially of a therapeutically effective amount of an N,N-bis(3-aminopropyl) C6-C18 alkyl amine, wherein the composition retains germicidal activity in the presence of greater than 10% manure.
In one embodiment, a method for treating or preventing infectious hoof diseases includes topically administering a therapeutically effective amount of an aqueous composition comprising an N,N-bis(3-aminopropyl) C6-C18 alkyl amine to one or more hooves of an animal, wherein the step of administering occurs with the hoof or hooves in a natural state.
DETAILED DESCRIPTION
There will now be shown and described compositions and methods for treating or preventing hoof diseases.
Concentrations disclosed throughout this application are based on ready-to-use compositions, except where otherwise stated. Those of skill in the art will appreciate that such compositions may be manufactured and/or sold in concentrated forms that are suitable for dilution prior to use. Manipulation of the concentration of the disclosed compositions is within the level of ordinary skill in the art.
In one embodiment, an aqueous composition for the treatment or prevention of infectious hoof diseases contains a germicide. The germicide may be present in an amount from about 0.03% to about 90% by weight of the composition, or from about 0.03% to about 50% by weight, or from about 0.03% to about 30% by weight, or from about 0.03% to about 2% by weight, or from about 0.1% to about 1% by weight, and may be used to treat animal hooves that are presented in their natural state. Hooves in their natural state may be soiled with particulate matter, such as dirt and manure, and/or microscopic pathogens, such as bacteria. For example, the present compositions remain effective in the presence of greater than 10% manure, or greater than 20% manure. Use of the present compositions on hooves in their natural state eliminates the need for a pre-treatment or pre-cleaning step, and therefore provides a significant cost and time advantage over known compositions.
In one embodiment, a composition for the treatment or prevention of hoof diseases comprises an effective amount of an N,N-bis(3-aminopropyl) C6-C18 alkyl amine, and optionally additional germicides selected from the group consisting of bronopol, chlorhexidine salts, C6-C12 fatty acids, triclosan, glycolic acid, lactic acid, polyhexamethyl biguanide, polyhexamethylene guanidine hydrochloride, polyhexamethylene guanidine hydrophosphate, poly[2-(2-ethoxy)-ethoxyethyl]-guanidinium chloride, benzyl alcohol, benzoic acid and mixtures thereof.
In another embodiment, an aqueous composition for the treatment or prevention of infectious hoof diseases consists essentially of an effective amount of an N,N-bis(3-aminopropyl) C6-C18 alkyl amine, and optionally additional ingredients that do not materially alter the germicidal properties of the composition. Such additional ingredients may include one or more of a pH adjusting agent, a wetting agent, a foaming agent, a dye, a viscosity control agent, a preservative, a skin conditioning agent, a coupling agent and a solvent.
Preferred compositions provide a substantial reduction, e.g., greater than 99% or preferably 99.99%, in Gram positive and Gram negative bacterial populations. Exemplary bacteria that contribute to hoof infections include Bacteroides spp, Bacteriodes melaningenicus, Campylobacter faecalis, Clostridium spp, Fusobacterium spp, Peptococcus asaccharolyticus, Peptostreptococcus spp, Serpens spp, Treponema spp, Bacteroides thetaictaomicron, Fusobacterium necrophorum, Prevotella melaminogenicus, Porphyromonas asaccharolytica, Porphyromonas levii, Porphyromonas melaminogenicus, Dichelobacter fragilis, Arcanobacterium pyogenes, Dichelobacter nodosus and Porphyromonas necrophorum. The quantity of a composition that achieves a substantial reduction in a bacterial population is considered an effective amount of the composition for treating or preventing infectious hoof diseases.
As discussed above, solutions for the treatment or prevention of infectious hoof diseases can be supplied either as ready-to-use products or as concentrates for dilution at the point of use. The compositions may be acidic (pH less than about 5) or near neutral with pH from about 5 to about 10. Generally, the pH may be adjusted to any value that is desired in the intended environment of use by the addition of acid, base or buffer.
A broader object of the disclosed instrumentalities is to provide a germicidal composition that may be used, for example, according to any purpose for antibacterial or bactericidal properties. In a particular embodiment, the composition is intended to be used as a footbath for treating animal hooves. In other embodiments the composition is intended to be used as a hand sanitizer, a skin cleanser, a surgical scrub, a wound care agent, a disinfectant, a bath/shower gel, a hard surface sanitizer and the like. Preferred compositions for skin applications have a pH of about 2.5 to about 10 and provide a substantial reduction, e.g., greater than 99%, in Gram positive and Gram negative bacterial populations. In even more preferred embodiments, the compositions have a pH in the range of about 5 to 10. Further, different uses may prompt different pH targets. For example, compositions adapted for hard surfaces may exhibit low pH values, such as 1.0 or 0.5.
The phrase “therapeutically effective amount” is intended to qualify the amount of the topical composition which will achieve the goal of decreased microbial concentration. “Therapeutically effective” may also refer to improvement in disorder severity or the frequency of incidence over no treatment.
The term “topical” shall refer to any composition which may be applied to the epidermis, keratin or other animal portion.
The term “additive” shall mean any component that is not a germicide or a solvent used to dilute or solubilize the components of the composition.
The germicidal activity of a large number of ingredients has been tested for the ability to kill Escherichia coli and Staphylococcus aureus in mixtures that have been contaminated with 10% and 20% manure. E. coli and S. aureus were chosen as representative bacteria for screening purposes. Solutions of the mixtures with 10% manure and bacteria were prepared, and the reduction in the concentration of bacteria was determined after 30 seconds and again after 5 minutes. In addition, the formulas were evaluated for skin irritation based on in vitro test data. The testing method used was that of Wolfgang J. W. Pape, Udo Hoppe: In vitro Methods for the Assessment of Primary Local Effects of Topically Applied Preparations. Skin Pharmacol. (1991), 4: 205-212, which is incorporated herein by reference. Based on this data, various components were selected for use in aqueous disinfectant solutions, such as footbaths.
Those of skill in the art will appreciate that variability in manure composition occurs due to differing diets, physiology, habitat, the presence or absence of diseases or pathogens and the like between animals. Trials conducted herein were performed in the presence of an exemplary manure sample, and showed excellent germicidal activity. If in practice, however, it becomes necessary to adjust the disclosed compositions to accommodate for variations in manure, such adjustment is within the level of skill of the ordinary artisan.
Germicides
A preferred composition includes from 0.001% to 90% by weight of at least one germicide. Throughout this disclosure, the term “germicide” shall be used to describe a composition which, when used alone or in combination with other germicides, accelerates the demise or limits the growth or replication of microorganisms, particularly bacteria. Examples of suitable germicides include N,N-bis(3-aminopropyl) C6-C18 alkyl amines (such as N,N-bis(3-aminopropyl)dodecylamine), bronopol (2-bromo-2-nitro-1,3-propanediol), chlorhexidine salts, C6-C12 fatty acids, triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether, may be purchased from Ciba Specialty Chemicals as IRGASAN™ and IRGASAN DP 300™), glycolic acid, lactic acid, benzyl alcohol, benzoic acid, polyhexamethyl biguanide (CAS 32289-58-0), guanidine salts such as polyhexamethylene guanidine hydrochloride (CAS 57028-96-3), polyhexamethylene guanidine hydrophosphate (89697-78-9), and poly[2-(2-ethoxy)-ethoxyethyl]guanidinium chloride (CAS 374572-91-5), and mixtures thereof. N,N-bis(3-aminopropyl)dodecylamine is a particularly preferred germicide.
In one embodiment, the disclosed germicides may be used in combination with traditional germicides such as copper sulfate, zinc sulfate, sulfamethazine, quaternary ammonium compounds, hydrogen peroxide and/or peracetic acid, for example, to achieve an effective kill at lower concentrations of traditional germicides.
Acids
In one embodiment, a composition includes from 0.2% to 90% by weight of at least one acid. Acids for use in the present compositions are selected for their efficacy against microorganisms, particularly bacteria, and minimal irritation of the skin. Examples of suitable acids include sulfuric acid, sulfurous acid, sulfamic acid, hydrochloric acid, phosphoric acid, phosphorous acid, C1-C4 fatty acids, citric acid, glycolic acid, lactic acid, acetic acid, benzoic acid, malic acid, oxalic acid, tartaric acid, succinic acid, glutaric acid, valeric acid and the like.
The aforementioned compositions may be supplemented by buffering agents, pH adjusting agents, emollients, preservatives, surfactants or wetting agents, dyes, foaming agents, viscosity modifying agents, stabilizers, perfumes, co-solvents, coupling agents and mixtures thereof. These may be present in any suitable amount.
pH Adjusting Agents
The pH value of the composition may be adjusted by the addition of acidic, basic or buffering agents. Suitable acids for use as pH adjusting agents may include, for example, sulfuric acid, sulfurous acid, sulfamic acid, hydrochloric acid, phosphoric acid, phosphorous acid, C1-C4 fatty acids, citric acid, glycolic acid, lactic acid, acetic acid, benzoic acid, malic acid, oxalic acid, tartaric acid, succinic acid, glutaric acid, valeric acid and the like. The pH may be raised, or made more alkaline, by addition of an alkaline agent such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate or combinations thereof. Traditional acid buffering agents such as citric acid, lactic acid and phosphoric acid may also be used to maintain a desired pH.
Wetting Agents
Wetting agents or surfactants may be included in the disclosed formulations. Typical wetting agents are used to wet the surface of application, thereby reducing surface tension so that the product can easily contact the surface. The wetting agents or surfactants of the formulation increase overall detergency of the formula, solubilize or emulsify organic ingredients that otherwise would not dissolve or emulsify, and facilitate penetration of active ingredients deep into depressions of the surface, which may be an animal hoof.
Suitably effective surfactants may include anionic, cationic, nonionic, zwitterionic and amphoteric surfactants. Wetting agents and surfactants suitable for use in the disclosed formulations can be high foaming, low foaming and non-foaming. Suitable anionic surfactants can be chosen from alkyl sulfonic acid, an alkyl sulfonate salt, a linear alkyl benzene sulfonic acid, a linear alkyl benzene sulfonate, an alkyl α-sulfomethyl ester, an α-olefin sulfonate, an alcohol ether sulfate, an alkyl sulfate, an alkylsulfo succinate, a dialkylsulfo succinate, or alkali metal, alkaline earth metal, amine and ammonium salts thereof. Specific examples are linear C10-C16 alkylbenzene sulfonic acid, linear C10-C16 alkylbenzene sulfonate or alkali metal, alkaline earth metal, amine and ammonium salts thereof, e.g., sodium dodecylbenzene sulfonate, sodium C14-C16 α-olefin sulfonate, sodium methyl α-sulfomethyl ester and disodium methyl α-sulfo fatty acid salts. Suitable nonionic surfactants can be chosen from alkyl polyglucoside, alkyl ethoxylated alcohol, alkyl propoxylated alcohol, ethoxylated-propoxylated alcohol, sorbitan, sorbitan ester and alkanol amide. Specific examples include C8-C16 alkyl polyglucoside with a degree of polymerization ranging from 1 to 3 e.g., C8-C10 alkyl polyglucoside with a degree of polymerization of 1.5 (Glucopon® 200), C8-C16 alkyl polyglucoside with a degree of polymerization of 1.45 (Glucopon® 425), C12-C16 alkyl polyglucoside with a degree of polymerization of 1.6 (Glucopon® 625), and polyethoxylated polyoxypropylene block copolymers (poloxamers) including by way of example the Pluronic® poloxamers commercialized by BASF Chemical Co. Amphoteric surfactants can be chosen from alkyl betaines and alkyl amphoacetates. Suitable betaines include cocoamidopropyl betaine, and suitable amphoacetates include sodium cocoamphoacetate, sodium lauroamphoacetate and sodium cocoamphodiacetate.
Foaming Agents
A foaming agent may be used in the disclosed antimicrobial compositions. A foaming agent aerates a liquid composition to produce a foam that may increase surface area of the composition and improve adherence with the surface to be treated (e.g., an animal hoof). Typically, a high foaming surfactant such as sodium lauryl sulfate, dodecylbenzene sulfonic acid, sodium alkylaryl polyether sulfate, sodium lauryl ether sulfate, sodium decyl sulfate, cocamine oxide, C12-C14 whole coconut amido betaines can be used to generate a stable foam. The foam is produced when agitation in the form of a compressed gas is mixed with the solution either by bubbling the gas into the solution or spraying the solution or solution-gas mixture through spray equipment. Suitable gases include but are not limited to nitrogen, air, carbon dioxide and mixtures thereof. Foam can also be generated by the mechanical action of animals walking through the composition, or by other mechanical means that mix atmospheric air with the composition. The composition can be applied by having animals walk through an area containing the foam or by having the animal walk through a footbath solution that has foam floating on top of the solution.
Dyes
One or more dyes may be included in the composition. Color on an animal's hoof or hooves may serve as an indicator that a particular animal has been treated. To preclude any problems with possible contamination of milk, for example, in the event that the dye contacts the animal's teats or enters the animal's circulatory system, only FD&C Certified (food grade) dyes should be used. There are many FD&C dyes available, such as FD&C Red #40, FD&C Yellow #6, FD&C Yellow #5, FD&C Green #3, FD&C Blue #1, FD&C Orange #4 and combinations thereof.
Viscosity Modifying Agents
Solution viscosity may be thinned by the addition of water or co-solvent; however, the compositions, especially gel forms, may benefit from the use of a viscosity modifying agent in an amount generally ranging from 0.1% to about 10% by weight of the composition. Viscosity of the composition preferably ranges from 1 cPs to 10000 cPs at ambient temperature. The viscosity referred to throughout this application is Brookfield viscosity measured in cPs by a Brookfield LV viscometer at ambient temperature (25° C.) with a spindle #2 @ 3 to 30 rpm. In various embodiments, a thickener may be added to achieve a viscosity range of from 50 cPs to 10000 cPs, or from 1000 cPs to 4000 cPs.
Viscosity modifying agents include plant gum materials such as guar gum; starch and starch derivatives, for example, hydroxyethyl starch or cross-linked starch; microbial polysaccharides, for example, xanthan gum or seaweed polysaccharides, such as sodium alginate, carrageenan, curdlan, pullulan or dextran; whey; gelatin; chitosan; chitosan derivatives; polysulfonic acids and their salts; polyacrylamide; and glycerol. Cellulosic thickeners may be used including hemicellulose, for example arabinoxylanes and glucomannanes; cellulose and derivatives thereof; for example methyl cellulose, ethyl cellulose, hydroxyethyl cellulose or carboxymethyl cellulose.
Preservatives
Preservatives may be added to the compositions. For example, ethylenediaminetetraacetic acid (EDTA) and its alkali salts act as chelating agents to bind metal ions that would otherwise facilitate metalloenzyme reactions that produce energy for bacterial cell replication. Other traditional preservatives are widely used, for example, paraban, methyl paraban, ethyl paraban, glutaraldehyde, etc. Preservatives such as an alcohol can also be added. The alcohol, in embodiments, may be benzyl alcohol, a low molecular weight alcohol having a carbon number less than five, and combinations thereof.
Skin Conditioning Agents
Skin conditioning agents may also be optionally used in the disclosed compositions. Skin conditioning agents may provide extra protection for human or animal skin prior to or subsequent to being exposed to adverse conditions. For example, skin conditioning agents may include moisturizers, such as glycerin, sorbitol, propylene glycol, Laneth-5 to 100, lanolin alcohol, shea butter and coco butter; sunscreen agents, such as titanium dioxide, zinc oxide, octyl methoxycinnamate (OMC), 4-methylbenzylidene camphor (4-MBC), avobenzone, oxybenzone and homosalate; and itch-relief or numbing agents, such as aloe vera, calamine, mint, menthol, caphor, antihistamines, corticosteroids, benzocaine and paroxamine HCl.
Coupling Agents
In some embodiments, a composition may contain a coupling agent that facilitates dissolution of one or more components, e.g., surfactants or fatty acids that would otherwise be insoluble or only sparingly soluble in the solvent. Coupling agents generally contain short chained (C2-C6) moieties linked to bulky hydrophilic groups, such as hydroxyl and/or sulfonate groups. Exemplary coupling agents include aryl sulfonates such as sodium naphthalene sulfonate, sodium octane sulfonate, sodium xylene sulfonate, and ammonium octane sulfonate, as well as some phosphate esters.
Solvents
The preferred solvent for the present composition is water. However, one skilled in the art will recognize that solvents or co-solvents other than water may be used to serve the same purpose. In some embodiments, a composition may contain at least about 5% by weight water and preferably at least about 10% by weight water based on the total weight of the composition. Propylene glycol, ethylene glycol, glycerine and alcohols can also be used as solvents either alone or in combination with water.
In one embodiment, a method for treating or preventing infectious hoof diseases includes topically administering a therapeutically effective amount of an aqueous germicidal composition comprising a germicide, or an acid and a germicide. The composition may be administered as a liquid, a spray, a foam, a gel, an ointment, a cream, a footbath, a footwrap coated with the composition, or any other topical form acceptable to the industry.
EXAMPLES Bacteria Testing
Experiments were performed to test the germicidal properties of the disclosed compositions using a modified version of the AOAC sanitizer test (Association of Official Analytical Chemists. 1990. Official Methods of Analysis, Pages 138-140 in Germicidal and Detergent Sanitizing Action of Disinfectants 960.09, Vol. I. 15th ed. AOAC, Arlington, Va.). According to this procedure, manure was collected from a dairy farm, dispensed into flasks and autoclaved at 121° C. and 17 psi for 30 minutes. Manure samples were then stored in a freezer until needed. When needed, manure was thawed at room temperature then dispensed into 250 mL Erlenmeyer flasks in amounts appropriate for the challenge desired (10 g for 10% manure, 20 g for 20% manure, etc.). The flasks with manure, and any empty flasks needed, were capped with aluminum foil and autoclaved at 134° C. and ˜20 psi for 4 min.
Freeze-dried pellets of E. coli (ATCC 11229) and S. aureus (ATCC 6538) were hydrated, placed in test tubes containing nutrient agar and incubated at 37° C. for 24 hours. Sterile buffer (0.0003 M phosphate adjusted to pH 6.6) was used to dilute and transfer the bacteria to additional nutrient agar tubes, which were incubated for another 24 hours. S. aureus was then diluted with buffer and transferred to nutrient agar in French bottles, and E. coli was diluted and transferred to fresh nutrient agar tubes. Both types of bacteria were incubated at 37° C. for 72 hours. E. coli was then diluted and transferred to nutrient agar in French bottles. Sterile buffer and glass beads were added to the S. aureus French bottles and the solution was vacuum filtered through a #2 filter. The resulting bacterial suspension had a concentration of approximately 108 cfu/mL. After 24 hours, the E. coli suspension was collected in the same manner.
Germicide sample solutions were prepared and dispensed into the flasks containing manure. For tests without manure, 99 mL of germicide were added to an empty, sterile, 250 mL flask. For a 10% manure challenge, 89 mL of germicide were added to a flask prepared with 10 g of manure, and 79 mL of germicide were added to flasks with 20 g of manure for a 20% manure challenge.
When all flasks with manure and germicide solution were prepared, 1 mL of approximately 108 cfu/mL bacteria suspension was mixed into the first test flask and a timer was started to monitor the contact time. After the desired contact time, 1 mL of the solution of bacteria, germicide and manure was added to a test tube containing 9 mL of a neutralizer appropriate for the germicide. For example, N,N-bis(3-aminopropyl)dodecylamine was neutralized with a peroxide neutralizer solution containing: tryptic soy powder 30 g/L; lecithin 30 g/L; Tween 80 100 g/L; sodium thiosulfate 5 g/L; and L-histidine 1 g/L diluted to 1 L in a volumetric flask. Three serial dilutions were made of this solution and 1 mL of each solution was dispensed into a Petri dish in duplicate. Also, 0.1 mL of the most dilute solution was dispensed in duplicate. Approximately 15 mL of sterile tryptone glucose extract agar was added to each Petri dish and when solidified, each plate was incubated at 37° C. for 48 hours. This procedure was repeated for all samples to be tested.
For controls, the 108 cfu/mL bacteria suspensions were diluted to concentrations of 104 and 103 cfu/mL. One milliliter of the 104 cfu/mL dilution and 0.1 mL of the 103 cfu/mL dilution (done in triplicate) were dispensed onto Petri dishes and approximately 15 mL of tryptone glucose extract agar was added. When solidified, the plates were incubated at 37° C. for 48 hours. An average of the plate counts for the triplicate platings of the 103 cfu/mL dilution was considered the initial numbers control count.
The results were obtained after 48 hours, all plates were counted following standard counting procedures. Percent reduction was calculated using the following formula:
( IC - SC ) * 100 IC ⁢ ⁢ where ⁢ : ⁢ ⁢ IC = Initial ⁢ ⁢ Numbers ⁢ ⁢ Control ⁢ ⁢ Count ⁢ ⁢ ( cfu / mL ) ⁢ SC = Test ⁢ ⁢ Substance ⁢ ⁢ Control ⁢ ⁢ Count ⁢ ⁢ ( cfu / mL )
The percent reduction was then converted into a log kill value.
Irritation Testing
Irritation tests were performed to determine whether or not the disclosed compositions would be mild enough for topical application. These tests involved two measurements made on fresh calf blood, where red blood cells were isolated by adding 50 mL of sodium citrate buffer (17.03 g trisodium citrate+8.45 g citric acid diluted to 1 L with bacteria-free DI water) to every 450 mL of blood, then repetitively washing with sodium citrate buffer and centrifuging to remove white blood cells and plasma.
Compositions disclosed herein were introduced into a container containing the isolated red blood cells and values for Haemolysis (H50); a Denaturation Index value (DI); and a Lysis/Denaturation Ratio (L/D) were determined using methods disclosed by Wolfgang J. W. Pape, Udo Hoppe: In vitro Methods for the Assessment of Primary Local Effects of Topically Applied Preparations. Skin Pharmacol. (1991), 4: 205-212. The haemolysis—or tendency of the red blood cells to rupture when in contact with the test product—was measured by the half-haemolysis value H50. The denaturation of protein caused by the test product was measured by the denaturation index (DI). The overall irritation value for a product was determined by the ratio of the H50/DI which is referred to as the lysis/denaturation quotient. The overall irritation score is given by the lysis/denaturation value which is calculated by the equation: L/D=H50 (measured in ppm)/DI (measured in %).
The H50 value which measures haemolysis alone usually shows a similar irritation correlation to the L/D ratio. The higher the ppm value for H50 the less irritating the product. A crude scale is H50>500 ppm (non-irritant); 120-500 (slight irritant), 30-120 (moderate irritant), 10-30 (irritant) and 0-10 (strong irritant).
The DI score which measures denaturation of protein also shows a correlation to the L/D ratio. A crude scale is DI 0-5% (non-irritant); 5-10% (slight irritant), 10-75% (moderate irritant), 75-100% (irritant) and >100% (strong irritant).
The L/D ratio is the primary value used to determine irritation. An L/D value greater than 100 is an indication that the formulation is a non-irritant; levels between 10 and 100 are considered slight irritants; levels between 1 and 10 are considered moderate irritants; levels between 0.1 to 1 are considered irritants; and levels lower than 0.1 are considered strong irritants. A practical upper limit for the L/D ratio is about 1,000,000.
Example 1
An 18% solution of N,N-bis(3-aminopropyl)dodecylamine when diluted 1+66 with potable water gave >8 log reduction (complete kill) for E. coli and S. aureus after 5 minutes exposure with no manure added. This Example shows that N,N-bis(3-aminopropyl)dodecylamine is effective at a concentration of only 0.27%.
Example 2
An 18% solution of N,N-bis(3-aminopropyl)dodecylamine when diluted 1+66 with potable water gave a >8 log reduction (complete kill) of E. coli and a 4.8 log reduction of S. aureus after 30 seconds exposure with 20% manure added. This Example shows that addition of 20% manure to a 0.27% N,N-bis(3-aminopropyl)dodecylamine solution (Example 1) has little affect on activity.
Example 3
An 18% solution of N,N-bis(3-aminopropyl)dodecylamine when diluted 1+180 with potable water gave >7.97 log reduction (complete kill) for E. coli and >7.94 log reduction for S. aureus after 5 minutes exposure with 10% manure added. This Example shows that N,N-bis(3-aminopropyl)dodecylamine has excellent germicidal properties at concentrations at least as low as 0.1%.
Example 4
An 18% solution of N,N-bis(3-aminopropyl)dodecylamine when diluted 1+33 with potable water gave >8.0 log reduction (complete kill) for E. coli and >7.94 log reduction for S. aureus after 5 minutes exposure with 20% manure added. This Example shows that N,N-bis(3-aminopropyl)dodecylamine has excellent germicidal properties even in the presence of 20% manure.
Example 5
An 18% solution of N,N-bis(3-aminopropyl)dodecylamine gave an H50 value of 18000 and a DI value of 2.6 with a combined L/D value of 7×103, which indicates that this solution does not cause skin irritation.
Example 6 Treponema Study
In an experiment carried out at the University of Liverpool, Liverpool, U.K., Treponema species were isolated from dairy farms and six cultures were used to measure the minimum inhibitory concentration (MIC, the lowest concentration which results in maintenance or reduction of inoculum's viability) and minimal bactericidal concentration (MBC, the lowest concentration which results in biocidal activity) of several commonly used germicides. The National Clinical Committee for Laboratory Standards (NCCLS) suggests that an agent is “bactericidal” when it causes a 3-log(99.9%) reduction in colony-forming units (cfu)/mL after 18 to 24 hours of incubation in liquid media.
Bacterial Isolates
Six Bovine Digital Dermatitis (BDD) associated treponeme strains (Table 1) were used to investigate in vitro susceptibility of BDD associated Treponema (Evans, N. J.; Brown, J.; Demirkan, I.; Carter, S. D.; Hart, C. A. “In vitro susceptibility of Bovine Digital Dermatitis associated Treponema to antimicrobial agents” to be submitted to Antimicrob. Agents Chemother. To be submitted for publication September 2007). The strains included two isolates from each of three distinct phylogroups corresponding to three proposed new taxa, Treponema medium subsp. bovis, Treponema bovis and Treponema pedis (Evans, N. J.; Brown, J.; Demirkan, I. Murray, R. D.; Vink, D.; Blowey, R. W.; Hart, C. A.; Carter, S. D. “Tremponema medium subsp. bovis subsp. nov., Treponema bovis sp. nov. and Treponema pedis sp. nov.; novel spirochaetes associated with Bovine Digital Dermatitis.” International Journal of Systematic and Evolutionary Microbiology. Submitted for publication Oct. 18, 2006). Two strains chosen for each of the three phylogroups were isolated from different regions in the United Kingdom.
TABLE 1
Strain Biopsy Date Location Serum Group
T19 1 Oct. 2003 Merseyside, RS T. medium
Farm 1, cow 2 subsp. bovis
T136E 28 Jan. 2004 Shropshire, Farm RS T. medium
1, cow 1 subsp. bovis
T320 18 Feb. 2004 Merseyside, FCS T. bovis
Farm 2, cow 1
G169A 16 May 2004 Gloucestershire, FCS T. bovis
Farm 3, cow 1
T3552B 17 Feb. 2004 Merseyside, FCS T. pedis
Farm 2, cow 4
G819CB 1 May 2004 Gloucesterdshire, FCS T. pedis
Farm 1, cow 1

Germicidal Susceptibility Testing
Germicidal susceptibility testing was performed using the broth microdilution method previously described by Evans et al., 2007. Ninety-six well sterile polystyrene microplates, each including positive controls (bacteria inoculated without germicide), negative controls (no bacteria or germicide) and serial two-fold dilutions of each composition to be tested, all in oral treponeme enrichment broth (OTEB; Anearobe Systems, CA, USA) inclusive of the respective serum supplement, were used. The respective OTEB serum supplements were 10% (v/v) fetal calf serum (FCS) for T. bovis and T. pedis strains and 10% (v/v) rabbit serum (RS) for T. medium subsp. bovis strains: Microplates were incubated in an anaerobic cabinet overnight prior to use. The T. pedis, T. medium subsp. bovis and T. bovis strain inoculums were taken from cultures grown for 4, 6 and 7 days respectively with all cultures being grown at 36° C. under anaerobic conditions in OTEB supplemented with respective serums. An inoculation volume of 50 μl was used for all three taxa. Each well, prior to inoculation, had a volume of 150 μl resulting in a final volume, after inoculation, of 200 μl.
To determine MIC values, absorbance at 540 nm was measured for the microplate wells using a Multiskan microtitre plate reader (Thermo Scientific, Hampshire, U.K.). Measurements were recorded before and after incubation at 36° C. under anaerobic conditions—three days for T. pedis strains and four days for T. bovis and T. medium subsp. bovis strains. The MIC for each germicide was taken as the lowest concentration of germicide that prevented growth. Cell growth was determined by comparison of the absorbance measurement immediately before and after incubation. The MIC values were taken as the median of three experiments performed on different days.
For determination of MBC values for each germicide, after MIC determination, 25 μl of culture from the MIC well and the next three wells of increased germicide concentration were subcultured to new wells containing 175 μl OTEB with the respective serum supplement but no germicide. Microplates were incubated for a further four days at 36° C. under anaerobic conditions. Growth was assessed using phase contrast microscopy. The MBC value was defined as the dilution that contained no treponeme cells in the subcultured media. The MBC values are reported as the median of three experiments performed on different days.
The average MBC for copper sulfate was 0.0054% w/w and the average MEC for formaldehyde was 0.0094% w/w. This confirms that copper sulfate and formaldehyde are effective against Treponema organisms. However, it was determined that N,N-bis(3-aminopropyl)dodecylamine was effective at a concentration about a factor of one lower. The MBC for N,N-bis(3-aminopropyl)dodecylamine was 0.00051% w/w.
Example 7 Field Trial
An 18% solution of N,N-bis(3-aminopropyl)dodecylamine with 0.17% FD&C Red #40 and 0.28% FD&C Yellow #5 was tested in a field trial at a commercial dairy farm. The product was diluted at a rate of 1+66 V/V and used to fill a hoof bath trough that the cows walked through as they left the milking parlor. A fresh hoof bath solution was prepared every day and the cows walked through the solution once each day of the week. For a month before the trial began no hoof bath treatment was applied to the cows. At the start of the trial a complete evaluation of the front and hind hooves was performed by a certified hoof trimmer, along with a veterinarian, who recorded the diseases observed in each hoof. The evaluation of the hooves was again performed after the hoof bath had been used for two months. All hooves that were present for both evaluations, and were not were not treated with antibiotics and wrapped at the first evaluation, were included in the data. Table 2 shows the results of the trial as broken down into individual diseases. The trial included 178 hooves.
TABLE 2
Primary Secondary
Evaluation Evaluation
Heel Erosion 43 25
Interdigital 2 0
Dermatitis
Foot Rot 0 0
White Line 0 1
Abscess
Digital Dermatitis 33 25
Total 78 51
A decrease in digital dermatitis and heel erosion was observed after two months of treatment. Overall, about a 35% reduction in the total number of hoof problems was observed. Forty percent of the hooves that had digital dermatitis at the beginning of the trial were cured of digital dermatitis after two months of treatment, while nearly ninety percent of the hooves that were not infected with digital dermatitis at the beginning of the trial did not develop any signs of digital dermatitis by the end of the two month treatment.
Example 8 Concentrates of Compositions with Germicide
Lower Range Upper Range
(% W/W) (% W/W)
Dilution Ratio 1 + 19 V/V 1 + 149 V/V
Buffering sulfuric acid, hydrochloric acid, 0 5
and pH citric acid, C1-C4 fatty acids,
adjusting glycolic acid, lactic acid,
agents phosphoric acid, sodium hydroxide,
potassium hydroxide, ammonium
hydroxide
Germicide bronopol, chlorhexidine salts, C6-C12 5 90
fatty acids, triclosan, glycolic
acid, lactic acid, polyhexamethyl
biguanide, polyhexamethylene
guanidine hydrochloride,
polyhexamethylene guanidine
hydrophosphate, poly [2-(2-
ethoxy)-ethoxyethyl]-guanidinium-
chloride, benzyl alcohol, benzoic
acid, N,N-bis(3-
aminopropyl)dodecylamine
Surfactant nonionic, anionic, cationic 0 20
Dye 0 2
Optional ingredients foaming agents, viscosity 0 20
modifying agents,
stabilizers, perfumes, co-
solvents, coupling agents,
buffers
Example 9 Ready to Use Compositions with Germicide
Lower Range Upper Range
(% W/W) (% W/W)
Buffering sulfuric acid, hydrochloric acid, 0 4.5
agents and citric acid, C1-C4 fatty acids,
pH adjusting glycolic acid, lactic acid,
agents phosphoric acid, sodium
hydroxide, potassium hydroxide,
ammonium hydroxide
Germicide bronopol, chlorhexidine salts, C6-C12 0.03 2.0
fatty acids, triclosan, glycolic
acid, lactic acid, polyhexamethyl
biguanide, polyhexamethylene
guanidine hydrochloride,
polyhexamethylene guanidine
hydrophosphate, poly [2-(2-
ethoxy)-ethoxyethyl]-
guanidinium-chloride, benzoic
acid, benzyl alcohol, N,N-bis(3-
aminopropyl)dodecylamine
Surfactant nonionic, anionic, cationic 0 1
Dye 0 0.1
Optional ingredients foaming agents, viscosity 0 1.25
modifying agents,
stabilizers, perfumes, co-
solvents, coupling agents,
buffers

Claims (8)

What is claimed is:
1. A method for treating an infectious hoof disease of an animal, comprising:
topically administering a therapeutically effective amount of an aqueous composition comprising an N,N-bis(3-aminopropyl) C6-C18 alkyl amine to one or more hooves of an animal,
wherein the step of administering occurs without pre-treatment or pre-cleaning of the hoof or hooves.
2. The method of claim 1, wherein the concentration of the N,N-bis(3-aminopropyl) C6-C18 alkyl amine ranges from 0.03% to 90% by weight.
3. The method of claim 1, wherein the concentration of the N,N-bis(3-aminopropyl) C6-C18 alkyl amine ranges from 0.03% to 2% by weight.
4. The method of claim 1, wherein the concentration of the N,N-bis(3-aminopropyl) C6-C18 alkyl amine ranges from 0.1% to 1% by weight.
5. The method of claim 1, wherein the N,N-bis(3-aminopropyl) C6-C18 alkyl amine comprises N,N-bis(3-aminopropyl)dodecylamine.
6. The method of claim 1, wherein the infectious hoof disease is selected from papillomatous digital dermatitis, interdigital phlegmon, interdigital dermatitis, laminitis, white line disease and heel erosion.
7. The method of claim 1, wherein the aqueous composition further comprises a germicide selected from the group consisting of bronopol, chlorhexidine salts, C6-C12 fatty acids, triclosan, glycolic acid, lactic acid, polyhexamethyl biguanide, polyhexamethylene guanidine hydrochloride, polyhexamethylene guanidine hydrophosphate, poly[2-(2-ethoxy)-ethoxyethyl]-guanidinium chloride, benzyl alcohol, benzoic acid and mixtures thereof.
8. The method of claim 1, wherein the composition is administered as one of a spray, a foam, a gel, an ointment, a cream, a footbath or a footwrap.
US12/440,405 2006-09-08 2007-09-10 Compositions for the treatment of hoof diseases Expired - Fee Related US8772341B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/440,405 US8772341B2 (en) 2006-09-08 2007-09-10 Compositions for the treatment of hoof diseases

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US84311306P 2006-09-08 2006-09-08
US88824307P 2007-02-05 2007-02-05
US12/440,405 US8772341B2 (en) 2006-09-08 2007-09-10 Compositions for the treatment of hoof diseases
PCT/US2007/078004 WO2008031090A1 (en) 2006-09-08 2007-09-10 Compositions for the treatment of hoof diseases

Publications (2)

Publication Number Publication Date
US20100286270A1 US20100286270A1 (en) 2010-11-11
US8772341B2 true US8772341B2 (en) 2014-07-08

Family

ID=38846863

Family Applications (4)

Application Number Title Priority Date Filing Date
US12/440,409 Active 2029-10-11 US8569373B2 (en) 2006-09-08 2007-09-10 Compositions comprising A C2-C14 carboxylic acid and a surfactant for treating hoof diseases
US12/440,412 Abandoned US20100234328A1 (en) 2006-09-08 2007-09-10 Antimicrobial Compositions And Related Methods
US12/440,405 Expired - Fee Related US8772341B2 (en) 2006-09-08 2007-09-10 Compositions for the treatment of hoof diseases
US14/741,701 Active US9750755B2 (en) 2006-09-08 2015-06-17 Antimicrobial compositions and related methods

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US12/440,409 Active 2029-10-11 US8569373B2 (en) 2006-09-08 2007-09-10 Compositions comprising A C2-C14 carboxylic acid and a surfactant for treating hoof diseases
US12/440,412 Abandoned US20100234328A1 (en) 2006-09-08 2007-09-10 Antimicrobial Compositions And Related Methods

Family Applications After (1)

Application Number Title Priority Date Filing Date
US14/741,701 Active US9750755B2 (en) 2006-09-08 2015-06-17 Antimicrobial compositions and related methods

Country Status (5)

Country Link
US (4) US8569373B2 (en)
EP (3) EP2086529B1 (en)
DK (2) DK2061454T3 (en)
PL (1) PL2061454T3 (en)
WO (3) WO2008031087A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10028924B2 (en) 2013-10-24 2018-07-24 Delaval Holding Ab Antimicrobial compositions

Families Citing this family (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI0408099B1 (en) 2003-03-05 2014-04-08 Byocoat Entpr Inc Antimicrobial Solution and Process
US20090035228A1 (en) * 2007-08-02 2009-02-05 Shanta Modak Skin and surface disinfectant compositions containing botanicals
US9687429B2 (en) * 2007-06-20 2017-06-27 The Trustees Of Columbia University In The City Of New York Antimicrobial compositions containing low concentrations of botanicals
US9981069B2 (en) 2007-06-20 2018-05-29 The Trustees Of Columbia University In The City Of New York Bio-film resistant surfaces
WO2008157092A1 (en) 2007-06-20 2008-12-24 The Trustees Of Columbia University In The City Of New York Bio-film resistant surfaces
US9511040B2 (en) 2007-06-20 2016-12-06 The Trustees Of Columbia University In The City Of New York Skin and surface disinfectant compositions containing botanicals
KR20110033981A (en) * 2008-06-24 2011-04-04 프레쉬 익스프레스 인코포레이티드 Peracid and 2-hydroxy organic acid compositions and methods for treating produce
NL1036275C2 (en) * 2008-12-03 2009-09-29 Desiree Snijders-Driessen Natural healing cream for e.g. horse, is prepared by including lauric acid, capric, caproic, caprylic, lavendula officinalis, spygium, teatree oil and colloidal silver
WO2010127231A2 (en) * 2009-05-01 2010-11-04 Signal Investment And Management Co. Moisturizing antimicrobial composition
US8911755B2 (en) * 2009-06-22 2014-12-16 Eq Ag Solutions Antimicrobial composition
WO2011002929A1 (en) * 2009-06-30 2011-01-06 The Trustees Of Columbia University In The City Of New York Antimicrobial/preservative compositions comprising botanicals
JP5655075B2 (en) * 2009-08-06 2015-01-14 アニトックス コーポレーション Preservatives for water and feed
US8496972B2 (en) * 2009-10-26 2013-07-30 John Alex Lopes Cleaning, disinfecting and microbicidal compositions
US9474729B2 (en) * 2010-01-14 2016-10-25 Hydromer, Inc. Topical antimicrobial compositions and methods of using same
US9918991B2 (en) * 2010-01-14 2018-03-20 Hydromer, Inc. Topical antimicrobial compositions and methods of using same
RU2551565C2 (en) 2010-01-29 2015-05-27 Геа Хоул Инк. Rotary milking station, kit for its mounting and methods of its mounting and operation
GB2486875A (en) * 2010-12-17 2012-07-04 Ronald Alexander Scot Young Acidic anti-pathogenic cleaning composition
US20120288488A1 (en) * 2011-01-09 2012-11-15 Noble Ion, Llc Compositions and Methods of Use for Livestock Pen Spray
WO2012151441A1 (en) * 2011-05-04 2012-11-08 Lincoln Manufacturing Inc. Natural antimicrobial compositions
NZ594450A (en) * 2011-08-05 2014-03-28 Donaghys Ind Ltd Antimicrobial composition
MX2014004618A (en) 2011-10-20 2014-05-27 Anitox Corp Antimicrobial formulations with pelargonic acid.
US9968101B2 (en) 2011-11-03 2018-05-15 The Trustees Of Columbia University In The City Of New York Botanical antimicrobial compositions
DK2773334T3 (en) 2011-11-03 2019-12-09 Univ Columbia COMPOSITION WITH EXTENDED ANTIMICROBIAL ACTIVITY
MX2014006542A (en) 2011-11-30 2014-07-09 Anitox Corp Antimicrobial mixture of aldehydes, organic acids and organic acid esters.
TW201330856A (en) 2011-12-06 2013-08-01 Univ Columbia Broad spectrum natural preservative composition
WO2013096577A1 (en) * 2011-12-22 2013-06-27 Contact Marketing Solutions Innovative Technologies Antimicrobial composition for animal welfare
US20130172415A1 (en) * 2011-12-29 2013-07-04 Rubbermaid Commercial Products/Us Triclosan-free antibacterial soap
WO2014088806A1 (en) * 2012-12-07 2014-06-12 Isp Investments Inc. An environment-friendly, biodegradable, voc-free, non-corrosive aqueous solution of 1, 2-benzisothiazolin-3-one (bit) and process for preparing the same
AU2013364412B2 (en) * 2012-12-21 2018-10-04 Delaval Holding Ab Germicidal compositions comprising carboxylic acid mixture and use as topical disinfectants
US8986747B2 (en) 2012-12-21 2015-03-24 Todd G. Allen Thrush treatment paste
US20160021842A1 (en) * 2013-03-08 2016-01-28 Willi Fuchs Mechanical milking system, device, procedure and use for dairy animals that allows inhibiting, and/or preventing the presence of infections due to mastitis, with surface fungicide, antibacterial, antivirus, and microbicide properties, wherein the surface comprises specific surface rugosity formed by a special alloy with copper content mostly
WO2014153293A1 (en) * 2013-03-18 2014-09-25 Aqua Access Llc Methods and apparatuses related to treatment in milking facilities
US9301935B2 (en) 2013-06-10 2016-04-05 Naeem Uddin Broad spectrum pharmacological composition for treatment of various infections and diseases and methods of use
US11110072B2 (en) 2013-06-10 2021-09-07 Greyfer Innova Pharma, Llc Broad spectrum pharmacological composition for treatment of various infections and diseases and methods of use
US10493050B2 (en) 2013-06-10 2019-12-03 Naeem Uddin Broad spectrum pharmacological composition for treatmentof various infections and diseases and methodsof use
US10646461B2 (en) 2013-06-10 2020-05-12 Naeem Uddin Broad spectrum pharmacological composition for treatment of various infections and diseases and methods of use
EP3027024B1 (en) * 2013-10-03 2017-07-26 Dow Global Technologies Llc Microbicidal composition comprising bronopol or dazomet
MX2016014186A (en) * 2014-03-28 2019-01-10 Curazene Llc Microbial-relief composition.
US9675535B2 (en) 2014-09-22 2017-06-13 Rubbermaid Commercial Products/Us Triclosan-free antibacterial soap
US10772343B2 (en) 2014-11-19 2020-09-15 Kansas State University Research Foundation Chemical mitigants in animal feed and feed ingredients
KR20170096032A (en) 2014-12-18 2017-08-23 에코랍 유에스에이 인코퍼레이티드 Generation of peroxyformic acid through polyhydric alcohol formate
EP3286137A4 (en) 2015-04-23 2019-01-30 Lawrence Carlson Stable electrolyte material containing same
KR20180102045A (en) * 2015-07-03 2018-09-14 타이그러스, 엘엘씨 Materials to improve the properties of topical or surface treatment compositions
US10463041B2 (en) 2015-09-17 2019-11-05 Ecolab Usa Inc. Triamine solidification using diacids
BR112018005033B8 (en) 2015-09-17 2022-03-15 Ecolab Usa Inc Methods of producing a solid triamine composition, and of cleaning, sanitizing and/or disinfecting
MX2018005402A (en) 2015-10-30 2018-08-01 Reckitt Benckiser Llc Treatment compositions providing an antimicrobial benefit.
WO2017204727A1 (en) * 2016-05-27 2017-11-30 Delaval Holding Ab Teat dip with residual efficacy
WO2018022016A1 (en) 2016-07-26 2018-02-01 Colgate-Palmolive Company Liquid cleansing compositions with an antibacterial system and method of manufacturing thereof
US11559053B1 (en) * 2016-09-23 2023-01-24 Specialty Sales, LLC Livestock footbath solutions and methods of use
CN110225746A (en) * 2016-11-09 2019-09-10 普罗维塔欧洲技术有限公司 For treating the anti-microbial agents of beast hoof infection
FR3063012A1 (en) * 2017-02-23 2018-08-24 Hydrachim DISINFECTANT AND FILMOGENIC COMPOSITION FOR APPLICATION AFTER TREATMENT ON A LACTIC ACID CONTAINING TRAY
EP3366279A1 (en) * 2017-02-23 2018-08-29 Hydrachim Disinfectant and film-forming composition intended for being applied after milking a teat, containing lactic acid
MX2020001923A (en) * 2017-08-25 2020-03-24 Unilever Ip Holdings B V An antimicrobial composition.
WO2019038049A1 (en) 2017-08-25 2019-02-28 Unilever N.V. An antimicrobial composition
CN111093370A (en) * 2017-09-15 2020-05-01 高乔工业股份有限公司 Antimicrobial compositions
BR112020005885A2 (en) 2017-09-26 2020-09-29 Ecolab Usa Inc. antimicrobial, virucide, solid antimicrobial and solid virucide compositions, and methods for using an antimicrobial composition and inactivating a virus.
US10779525B2 (en) 2018-01-16 2020-09-22 Zin Research LLC Treatment compound and method of application for hoof or foot disease in animals
RU2699353C1 (en) * 2018-03-02 2019-09-05 Федеральное государственное бюджетное образовательное учреждение высшего образования Санкт-Петербургская государственная академия ветеринарной медицины (ВПО СПбГ ГАВМ) Method for preventing lactation mastitis in cows
US11260040B2 (en) 2018-06-15 2022-03-01 Ecolab Usa Inc. On site generated performic acid compositions for teat treatment
MX2021000984A (en) 2018-07-31 2021-04-12 Kimberly Clark Co Composition including an antimicrobial boosting agent including an amphocarboxylate and methods of increasing the antimicrobial effectiveness of a composition.
BR112021006553A2 (en) * 2018-12-04 2021-07-13 Virox Technologies Inc. antimicrobial compositions containing c3-c5 n-alkyl-gamma-butyrolactam and uses thereof
EP3890484A1 (en) * 2018-12-05 2021-10-13 DeLaval Holding AB Teat disinfectant composition
US10952430B2 (en) * 2019-02-06 2021-03-23 Virox Technologies Inc. Shelf-stable antimicrobial compositions
BE1027037B1 (en) 2019-02-08 2020-09-07 Nutrition Sciences Nv COMPOSITION FOR THE TREATMENT AND / OR PREVENTION OF INFECTIOUS HORSESHOE DISEASES
WO2021209108A1 (en) * 2020-04-14 2021-10-21 Panzerglass A/S Cleaning composition with disinfectant properties
CN111573801B (en) * 2020-04-30 2023-01-06 云浮市郁南县春旭环保科技有限责任公司 Organic composite aluminum sulfate water treatment agent and preparation method thereof
WO2021259215A1 (en) * 2020-06-22 2021-12-30 Rht Limited Antiseptic compositions
EP4082528A1 (en) * 2021-04-30 2022-11-02 GSK Consumer Healthcare SARL Liquid spray formulation
CA3217653A1 (en) * 2021-06-04 2022-12-08 Alan Edward Sherry Antimicrobial composition
EP4098121A1 (en) * 2021-06-04 2022-12-07 The Procter & Gamble Company Antimicrobial composition
WO2024091161A1 (en) * 2022-10-28 2024-05-02 Delaval Holding Ab Antimicrobial compositions

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6382136B1 (en) * 1998-11-17 2002-05-07 Henkel Ecolab Gmbh & Co. Ohg Method for treating the hooves of mammals especially cattle

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2739922A (en) 1952-03-13 1956-03-27 Herman A Shelanski Mixtures of polymeric n-vinyl pyrrolidone and halogens
GB734624A (en) 1952-11-21 1955-08-03 Mo Och Domsjoe Ab Bactericidal and similar compositions comprising cellulose ether carrier material
US3993777A (en) 1975-08-12 1976-11-23 Bio-Lab, Inc. Aqueous compositions to aid in the prevention of bovine mastitis
US4113854A (en) 1977-01-10 1978-09-12 Minnesota Mining And Manufacturing Company Prophylactic treatment of mastitis
US4199602A (en) 1978-02-23 1980-04-22 Economics Laboratory, Inc. Control of mastitis and compositions therefor
US4975217A (en) * 1981-07-20 1990-12-04 Kimberly-Clark Corporation Virucidal composition, the method of use and the product therefor
US4434181A (en) 1981-12-07 1984-02-28 Fearing Manufacturing Co., Inc. Teat dip
US4945110A (en) 1987-06-15 1990-07-31 Quali Tech, Inc. Membrame-forming veterinary antibacterial teat dip
US5225096A (en) 1989-05-18 1993-07-06 Colgate Palmolive Company Linear viscoelastic aqueous liquid automatic dishwasher detergent composition having improved chlorine stability
US5143720A (en) * 1990-11-28 1992-09-01 Microcide, Inc. Disinfecting and sanitizing compositions
WO1998016192A1 (en) 1996-10-17 1998-04-23 Alterna, Inc. Germicidal composition
US6436444B1 (en) 1997-09-26 2002-08-20 Ecolab Inc. Acidic aqueous chlorite teat dip providing shelf life sanitizing capacity and tissue protection
EP1027827A1 (en) * 1998-05-28 2000-08-16 Mandalay Inversiones, S.L. Disinfectant composition
US6346279B1 (en) 1998-12-14 2002-02-12 Virox Technologies, Inc. Hydrogen peroxide disinfectant with increased activity
US6686324B2 (en) * 1999-11-26 2004-02-03 Virox Technologies, Inc. Low-foaming hydrogen peroxide cleaning solution for organic soils
CA2407098C (en) * 2000-04-28 2009-12-29 Ecolab Inc. Antimicrobial composition
CA2410796C (en) * 2000-06-05 2007-05-01 S.C. Johnson & Son, Inc. Biocidal cleaning method
US6953772B2 (en) * 2000-07-18 2005-10-11 Lopes John A Concentrated sanitizing compositions for cleaning food and food contact surfaces
US6582734B1 (en) * 2000-07-20 2003-06-24 Ecolab Inc. Antimicrobial composition useful for the treatment of bovine mastitis
US6444707B1 (en) * 2000-08-22 2002-09-03 West Agro Topically applied hoof treatment composition and concentrate
US6663902B1 (en) * 2000-09-19 2003-12-16 Ecolab Inc. Method and composition for the generation of chlorine dioxide using Iodo-Compounds, and methods of use
WO2003003832A1 (en) * 2001-07-06 2003-01-16 Rnl Life Science Ltd. Acid disinfectant composition comprising an anion surfactant
US6627593B2 (en) * 2001-07-13 2003-09-30 Ecolab Inc. High concentration monoester peroxy dicarboxylic acid compositions, use solutions, and methods employing them
GB2379223A (en) * 2001-08-31 2003-03-05 Reckitt Benckiser Inc Cleaning composition comprising citric acid
CA2361741C (en) * 2001-11-14 2005-04-19 Virox Technologies Inc. Low-foaming hydrogen peroxide cleaning formulation for organic soils
US6472358B1 (en) * 2001-11-15 2002-10-29 Ecolab Inc. Acid sanitizing and cleaning compositions containing protonated carboxylic acids
EP1473998B1 (en) 2002-02-12 2016-12-07 Virox Technologies Inc. Enhanced activity hydrogen peroxide disinfectant
EP1483363B1 (en) * 2002-02-22 2006-11-29 Colgate-Palmolive Company Antibacterial cleaning wipe
CA2454437C (en) * 2003-12-30 2013-02-26 Virox Technologies Inc. Low-foaming hydrogen peroxide cleaning solution for organic soils
US7494963B2 (en) 2004-08-11 2009-02-24 Delaval Holding Ab Non-chlorinated concentrated all-in-one acid detergent and method for using the same
US8778369B2 (en) 2005-07-29 2014-07-15 Delaval Holding Ab Barrier film-forming compositions and methods of use
US20070027119A1 (en) * 2005-07-29 2007-02-01 Ahmed Fahim U Antibacterial composition and method of use
CN101309677B (en) * 2005-11-23 2011-03-09 韩国农村振兴厅 Cleaner for precaution against of cow's hoof, manufacturing method thereof, and using method thereof
WO2008061375A1 (en) * 2006-11-24 2008-05-29 Germiphene Corporation Antiseptic

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6382136B1 (en) * 1998-11-17 2002-05-07 Henkel Ecolab Gmbh & Co. Ohg Method for treating the hooves of mammals especially cattle

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10028924B2 (en) 2013-10-24 2018-07-24 Delaval Holding Ab Antimicrobial compositions

Also Published As

Publication number Publication date
DK2086529T3 (en) 2015-05-04
EP2061454A1 (en) 2009-05-27
WO2008031087A1 (en) 2008-03-13
WO2008031104A2 (en) 2008-03-13
DK2061454T3 (en) 2018-07-16
US20100234328A1 (en) 2010-09-16
US9750755B2 (en) 2017-09-05
EP2061447A1 (en) 2009-05-27
EP2086529A2 (en) 2009-08-12
PL2061454T3 (en) 2018-09-28
WO2008031104A3 (en) 2009-08-13
WO2008031090A1 (en) 2008-03-13
US20150272969A1 (en) 2015-10-01
EP2086529B1 (en) 2015-04-01
US20100234460A1 (en) 2010-09-16
US20100286270A1 (en) 2010-11-11
US8569373B2 (en) 2013-10-29
EP2061454B1 (en) 2018-06-06

Similar Documents

Publication Publication Date Title
US8772341B2 (en) Compositions for the treatment of hoof diseases
US10441557B2 (en) Germicidal compositions comprising carboxylic acid mixture and use as topical disinfectants
EP1740166B1 (en) Therapeutic antimicrobial compositions and methods
US20070249712A1 (en) Peracetic teat dip
EP3060040B1 (en) Antimicrobial compositions
WO2008031105A1 (en) Polymeric guanidine salt-based germicides
US20060177518A1 (en) Peracetic teat dip
US6525071B2 (en) Compositions and methods for the treatment and prevention of bovine mastitis
WO2007016067A2 (en) Antibacterial composition and method of use
US20040091553A1 (en) Composition and method for mammary disinfection during winter conditions
WO2024091161A1 (en) Antimicrobial compositions

Legal Events

Date Code Title Description
AS Assignment

Owner name: DELAVAL HOLDING AB, SWEDEN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FORET, CHRIS;SKENDER, ALEX;HEMLING, THOMAS C.;REEL/FRAME:024452/0736

Effective date: 20100519

FEPP Fee payment procedure

Free format text: MAINTENANCE FEE REMINDER MAILED (ORIGINAL EVENT CODE: REM.)

LAPS Lapse for failure to pay maintenance fees

Free format text: PATENT EXPIRED FOR FAILURE TO PAY MAINTENANCE FEES (ORIGINAL EVENT CODE: EXP.)

STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362

FP Lapsed due to failure to pay maintenance fee

Effective date: 20180708